One method of separating chemical compounds is chromatography wherein the compounds are separated based upon their different adsorption properties. However, chemical compounds, which have similar chemical structures, are difficult to separate with chromatography due to their similar properties such as adsorption. One example of this is exhibited in the difficulty in purifying a viable product, 6-O-methyl erythromycin A (Clarithromycin) from the impurity, 6,11-O-methyl erythromycin A. Clarithromycin is an effective antibiotic obtained by the chemical methylation of erythromycin, a naturally occurring antibiotic.
U.S. Pat. No. 4,990,602 to Morimoto et al. discloses the preferred commercial method for producing Clarithromycin by the chemical methylation of erythromycin. The methylation process used to produce Clarithromycin produces several by-products. A major by-product is 6,11-O-methyl erythromycin A (6, 11) which differs from Clarithromycin by the addition of an extra methyl group at the #11 carbon atom. The similar chemical structure between Clarithromycin and 6,11 increases the difficulty in separating the product, Clarithromycin and the by-product, 6,11. Therefore, in order to produce a high purity of Clarithromycin, a significant portion of Clarithromycin is left behind with the 6,11 resulting in a loss of Clarithromycin yield. Approximately seven percent of Clarithromycin is left behind in a mixture from the commercial process with the 6,11.
The mixture of Clarithromycin and 6,11 may be recovered in a nearly one-to-one solid mixture of Clarithromycin and 6,11. This solid mixture may contain up to 23% other impurities. These additional impurities are easily separated from Clarithromycin by crystallization.
Additional methods for the production of Clarithromycin are disclosed in U.S. Pat. No. 4,331,803 to Watanabe et al; U.S. Pat. No. 4,668,776 to Yamada et al.; U.S. Pat. No. 4,670,549 to Morimoto et al.; U.S. Pat. No. 4,672,109 to Watanabe et al.; U.S. Pat. No. 4,680,386 to Morimoto et al.; and U.S. Pat. No. 5,274,085 Amano et al.
A need exists for a method and apparatus to recover a high purity of Clarithromycin from the mixture of Clarithromycin and 6,11 left over from the commercial process in order to increase overall product yield of Clarithromycin.